Reverse Pharmacology

Question 1

What is the first example of reverse pharmacology ?

Answer 1

The discovery of Nociceptin

Question 2

What is the difference between reverse pharmacology and the classical approach ?

Answer 2

• In the classical approach pharmacology takes place first, followed by genomics
• Reverse pharmacology starts with genomics followed by pharmacology

Question 3

What are the three main steps in forward pharmacology ?

Answer 3

• Analysis of the functional activity e.g. of extracts or natural products (in vivo or in vitro)
• Identification of the lead compounds
• Target identification

Question 4

What are the three main steps in reverse pharmacology ?

Answer 4

• Identification of promising target proteins
• Screening for compounds interacting with the target protein
• Analysis of their functional activity in vivo

Question 5

How big is the human genome (in nucleotides) ?

Answer 5

3*10^9 nucleotides

Question 6

How many protein-coding genes contains the human genome ?

Answer 6

20.000 - 25.000

Question 7

What is a drug target ?

Answer 7

A drug target is a pharmacological receptor which is bind specifically by a drug.

Question 8

Name the four main kinds of drug targets.

Answer 8

• Physiological receptors
• Ion channels
• Enzymes
• Carrier molecules

Question 9

Which kind of protein comprises the largest group of drug targets ?

Answer 9

GPCRs
G-protein coupled receptors

Question 10

Name two molecular biological methods to identify nucleotide sequence homologies.

Answer 10

• Hybridization at low stringency (old fashion)
• PCR from cDNA or genomic DNA

Question 11

What are Orexins and Orexin receptors ?

Answer 11

• A family of hypothalamic neuropeptides and GPCRs
• They regulate feeding behaviour

Question 12

Which peptides does Prepro-Orexin contain ?

Answer 12

• OX1-Receptor
• OX2-Receptor

Both of them are GPCRs

Question 13

How is Narcolepsy caused ?

Answer 13

• By OX2-Receptor mutations in dogs
• By orexin-“knockout” in mice
• Lack of orexin neurons in humans

Question 14

Name five systems which are influenced by the central orexin system.

Answer 14

• Neuroendocrine functions
• Sleep-wake rhythm
• Reward system
• Energy balance
• Autonomic nervous system

Question 15

What are orexin receptor agonists ?

Answer 15

• Molecules activating the orexin receptor
• Usually peptides e.g. orexin A or B
• They are receptor subtype selective

Question 16

What is the OX1-Receptor binding ?

Answer 16

Orexin A

Question 17

What is the OX2-Receptor binding ?

Answer 17

Orexin A and Orexin B

Question 18

What is Danavorexton ?

Answer 18

• Selective OX2-Receptor agonist
• Used for the treatment of narcolepsy, idiopathic hypersomnia and sleep apnea

Question 19

Name three selective OX2-Receptor agonists.

Answer 19

• Danavorexton
• Firazorexton
• Oveporexton

Question 20

For the treatment of which kind of diseases are Orexin receptor agonists used ?

Answer 20

• Narcolepsy
• Metabolic diseases

Question 21

For the treatment of which disease are Orexin receptor antagonists used ?

Answer 21

Insomnia

Question 22

Name one non-selective, non-peptide Orexin-receptor antagonist.

Answer 22

Almorexant

Question 23

Name two selective, non-peptide Orexin-receptor antagonists.

Answer 23

• Nivaworexant
• Tebideutorexant

Question 24

Name four transmitters identified as ligands of orphan GPCRs.

Answer 24

• Nociceptin
• Ghrelin
• Metastin
• Succinate